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School

University of California - Irvine

Department

Biological Sciences

Course

BIO SCI M114

Professor

Alexander Mc Pherson

Semester

Spring

Description

Lecture 7 02/05/2014
Protein Structure & Protein Folding
Amphensen's dogma - 3D structure of protein = function
Disulfide bonds on ribonuclease
Though this is not always true, not all proteins can be denatured and refolded
Looking at all the hemoglobin, the 3D structure for all of them look very similar
The backbone is very similar in size & shape
But the variation of amino acid sequence also matters
This tells us that different sequence of amino acids can produce a similar structure
The high identity among protein tells us that they produce a similar structure
Thus there is a tremendous redundancy across proteins, as long as the structure is okay and
key amino acids in the important location, the backbone sequence may not have to be exactly
the same
Conserved Residues are regions where His (the active site) and the Cysteine (S-S)
We can determine the phylogenetic relationship by looking at the redundancy of amino acid
sequence across species
Divergent Evolution
Start with a precursor (primordial Dehydroenase)
Then Diverges, creates similar but different Dehydrogenases with similar function Lecture 7
Convergent Evolution
Trypsin: digests meat
Looking at Trypsin, there are 3 conserved residues that perform the catalytic activity
Looking at E. Sutlus: the 3 key residues are in the same place, but the rest of the sequence is
much different
We know that Humans are not from E. Sutulus, but this tells us that there is an ideal
constellation (specific residues) that gives the best conditions for a catalytic reaction
Gene Duplication
An organism has 2 genes that are similar
One of the genes mutates
The mutation allows for a new biochemical activity
Gene Fusion
A transposition of 1 gene, close to another one
During transcription, both genes are transcribed together forming 1 peptide
This allows for new Biochemical Function
Margoliask
Sequenced Cytochrome C
Present in all organism
104 residues in animals, 112 plant, 108 yeast
From 50 different species, 27aa are invariant (the same) Lecture 7
This tells us these 27aa are necessary
This does not tell us that we can any aa in the rest of the structure
Residue differences between species is proportional to phylogenetic differences
Protein Folding Problem
Not all proteins will fold without Chaperone proteins
These produce a special container, and a special environment for folding
We don't actually know how protein structure is determined by AA sequence
How it came about?
Heat shocked flies, and these flies produced Chaperones
Anthensen's experiment is not always true
Membrane proteins also do not fold by themselves
They only fold properly if they fold in a lipid environment
This is what the rough ER does
Hemoglobin will not fold properly unless in the presence of the heme
What do proteins look like?
Ribbon structure?
Beads on a string?